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Rosenberg JS, Cross FR, Funabiki H
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KNL1/Spc105 Recruits PP1 to Silence the Spindle Assembly Checkpoint
CURRENT BIOLOGY 2011 JUN 7; 21(11):942-947
The spindle assembly checkpoint (SAC) delays anaphase onset until kinetochores accomplish bioriented microtubule attachments [1]. Although several centromeric and kinetochore kinases, including Aurora B, regulate kinetochore-microtubule attachment and/or SAC activation [2-4], the molecular mechanism that translates bioriented attachment into SAC silencing remains unclear [5]. Employing a method to rapidly induce exact gene replacement in budding yeast [6], we show here that the binding of protein phosphatase 1 (PP1/GIc7) to the evolutionarily conserved RVSF motif of the kinetochore protein Spc105 (KNL1/Blinkin/CASC5) is essential for viability by silencing the SAC, while it plays an auxiliary nonessential role for physical chromosome segregation. Although Aurora B may inhibit this binding, persistent PP1-Spc105 interaction does not affect chromosome segregation and is insufficient to silence the SAC in the absence of microtubules, indicating that dynamic regulation of this interaction is dispensable. However, the amount of PP1 targeted to kinetochores must be finely tuned, because recruitment of either no or one extra copy of PP1 to Spc105 is detrimental, illustrating the vital impact of targeting an exiguous fraction of PP1 to the kinetochore. We propose that the PP1-Spc105 interaction enables local regulation of dynamic phosphorylation and dephosphorylation at the kinetochore to couple microtubule attachment and SAC silencing.
Aaltonen T, Gonzalez BA, Amerio S, Amidei D, Anastassov A, Annovi A, Antos J, Apollinari G, Appel JA, Apresyan A, Arisawa T, Artikov A, Asaadi J, Ashmanskas W, Auerbach B, Aurisano A, Azfar F, Badgett W, Barbaro-Galtieri A, Barnes VE, Barnett BA, Barria P, Bartos P, Bauce M, Bauer G, Bedeschi F, Beecher D, Behari S, Bellettini G, Bellinger J, Benjamin D, Beretvas A, Bhatti A, Binkley M, Bisello D, Bizjak I, Bland KR, Blumenfeld B, Bocci A, Bodek A, Bortoletto D, Boudreau J, Boveia A, Brau B, Brigliadori L, Brisuda A, Bromberg C, Brucken E, Bucciantonio M, Budagov J, Budd HS, Budd S, Burkett K, Busetto G, Bussey P, Buzatu A, Calancha C, Camarda S, Campanelli M, Campbell M, Canelli F, Canepa A, Carls B, Carlsmith D, Carosi R, Carrillo S, Carron S, Casal B, Casarsa M, Castro A, Catastini P, Cauz D, Cavaliere V, Cavalli-Sforza M, Cerri A, Cerrito L, Chen YC, Chertok M, Chiarelli G, Chlachidze G, Chlebana F, Cho K, Chokheli D, Chou JP, Chung WH, Chung YS, Ciobanu CI, Ciocci MA, Clark A, Compostella G, Convery ME, Conway J, Corbo M, Cordelli M, Cox CA, Cox DJ, Crescioli F, Almenar CC, Cuevas J, Culbertson R, Dagenhart D, d'Ascenzo N, Datta M, de Barbaro P, De Cecco S, De Lorenzo G, Dell'Orso M, Deluca C, Demortier L, Deng J, Deninno M, Devoto F, d'Errico M, Di Canto A, Di Ruzza B, Dittmann JR, D'Onofrio M, Donati S, Dong P, Dorigo M, Dorigo T, Ebina K, Elagin A, Eppig A, Erbacher R, Errede D, Errede S, Ershaidat N, Eusebi R, Fang HC, Farrington S, Feindt M, Fernandez JP, Ferrazza C, Field R, Flanagan G, Forrest R, Frank MJ, Franklin M, Freeman JC, Funakoshi Y, Furic I, Gallinaro M, Galyardt J, Garcia JE, Garfinkel AF, Garosi P, Gerberich H, Gerchtein E, Giagu S, Giakoumopoulou V, Giannetti P, Gibson K, Ginsburg CM, Giokaris N, Giromini P, Giunta M, Giurgiu G, Glagolev V, Glenzinski D, Gold M, Goldin D, Goldschmidt N, Golossanov A, Gomez G, Gomez-Ceballos G, Goncharov M, Gonzalez O, Gorelov I, Goshaw AT, Goulianos K, Gresele A, Grinstein S, Grosso-Pilcher C, Group RC, da Costa JG, Gunay-Unalan Z, Haber C, Hahn SR, Halkiadakis E, Hamaguchi A, Han JY, Happacher F, Hara K, Hare D, Hare M, Harr RF, Hatakeyama K, Hays C, Heck M, Heinrich J, Herndon M, Hewamanage S, Hidas D, Hocker A, Hopkins W, Horn D, Hou S, Hughes RE, Hurwitz M, Husemann U, Hussain N, Hussein M, Huston J, Introzzi G, Iori M, Ivanov A, James E, Jang D, Jayatilaka B, Jeon EJ, Jha MK, Jindariani S, Johnson W, Jones M, Joo KK, Jun SY, Junk TR, Kamon T, Karchin PE, Kato Y, Ketchum W, Keung J, Khotilovich V, Kilminster B, Kim DH, Kim HS, Kim HW, Kim JE, Kim MJ, Kim SB, Kim SH, Kim YK, Kimura N, Kirby M, Klimenko S, Kondo K, Kong DJ, Konigsberg J, Kotwal AV, Kreps M, Kroll J, Krop D, Krumnack N, Kruse M, Krutelyov V, Kuhr T, Kurata M, Kwang S, Laasanen AT, Lami S, Lammel S, Lancaster M, Lander RL, Lannon K, Lath A, Latino G, Lazzizzera I, LeCompte T, Lee E, Lee HS, Lee JS, Lee SW, Leo S, Leone S, Lewis JD, Lin CJ, Linacre J, Lindgren M, Lipeles E, Lister A, Litvintsev DO, Liu C, Liu Q, Liu T, Lockwitz S, Lockyer NS, Loginov A, Lucchesi D, Lueck J, Lujan P, Lukens P, Lungu G, Lys J, Lysak R, Madrak R, Maeshima K, Makhoul K, Maksimovic P, Malik S, Manca G, Manousakis-Katsikakis A, Margaroli F, Marino C, Martinez M, Martinez-Ballarin R, Mastrandrea P, Mathis M, Mattson ME, Mazzanti P, McFarland KS, McIntyre P, McNulty R, Mehta A, Mehtala P, Menzione A, Mesropian C, Miao T, Mietlicki D, Mitra A, Miyake H, Moed S, Moggi N, Mondragon MN, Moon CS, Moore R, Morello MJ, Morlock J, Fernandez PM, Mukherjee A, Muller T, Murat P, Mussini M, Nachtman J, Nagai Y, Naganoma J, Nakano I, Napier A, Nett J, Neu C, Neubauer MS, Nielsen J, Nodulman L, Norniella O, Nurse E, Oakes L, Oh SH, Oh YD, Oksuzian I, Okusawa T, Orava R, Ortolan L, Griso SP, Pagliarone C, Palencia E, Papadimitriou V, Paramonov AA, Patrick J, Pauletta G, Paulini M, Paus C, Pellett DE, Penzo A, Phillips TJ, Piacentino G, Pianori E, Pilot J, Pitts K, Plager C, Pondrom L, Potamianos K, Poukhov O, Prokoshin F, Pronko A, Ptohos F, Pueschel E, Punzi G, Pursley J, Rahaman A, Ramakrishnan V, Ranjan N, Redondo I, Renton P, Rescigno M, Rimondi F, Ristori L, Robson A, Rodrigo T, Rodriguez T, Rogers E, Rolli S, Roser R, Rossi M, Rubbo F, Ruffini F, Ruiz A, Russ J, Rusu V, Safonov A, Sakumoto WK, Sakurai Y, Santi L, Sartori L, Sato K, Saveliev V, Savoy-Navarro A, Schlabach P, Schmidt A, Schmidt EE, Schmidt MP, Schmitt M, Schwarz T, Scodellaro L, Scribano A, Scuri F, Sedov A, Seidel S, Seiya Y, Semenov A, Sforza F, Sfyrla A, Shalhout SZ, Shears T, Shepard PF, Shimojima M, Shiraishi S, Shochet M, Shreyber I, Simonenko A, Sinervo P, Sissakian A, Sliwa K, Smith JR, Snider FD, Soha A, Somalwar S, Sorin V, Squillacioti P, Stancari M, Stanitzki M, Denis RS, Stelzer B, Stelzer-Chilton O, Stentz D, Strologas J, Strycker GL, Sudo Y, Sukhanov A, Suslov I, Takemasa K, Takeuchi Y, Tang J, Tecchio M, Teng PK, Thom J, Thome J, Thompson GA, Thomson E, Ttito-Guzman P, Tkaczyk S, Toback D, Tokar S, Tollefson K, Tomura T, Tonelli D, Torre S, Torretta D, Totaro P, Trovato M, Tu Y, Ukegawa F, Uozumi S, Varganov A, Vazquez F, Velev G, Vellidis C, Vidal M, Vila I, Vilar R, Vizan J, Vogel M, Volpi G, Wagner P, Wagner RL, Wakisaka T, Wallny R, Wang SM, Warburton A, Waters D, Weinberger M, Wester WC, Whitehouse B, Whiteson D, Wicklund AB, Wicklund E, Wilbur S, Wick F, Williams HH, Wilson JS, Wilson P, Winer BL, Wittich P, Wolbers S, Wolfe H, Wright T, Wu X, Wu Z, Yamamoto K, Yamaoka J, Yang T, Yang UK, Yang YC, Yao WM, Yeh GP, Yi K, Yoh J, Yorita K, Yoshida T, Yu GB, Yu I, Yu SS, Yun JC, Zanetti A, Zeng Y, Zucchelli S
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Top quark mass measurement using the template method at CDF
PHYSICAL REVIEW D 2011 JUN 3; 83(11):? Article 111101
We present a measurement of the top quark mass in the lepton + jets and dilepton channels of t (t) over bar decays using the data sample corresponding to an integrated luminosity of 5.6 fb(-1) of p (p) over bar collisions at Tevatron with root s = 1.96 TeV, collected with the CDF II detector. We construct templates of two reconstructed top quark masses from different jets-to-quarks combinations and the invariant mass of two jets from the W decays in the lepton + jets channel, and a reconstructed top quark mass and m(T2), a variable related to the transverse mass in events with two missing particles, in the dilepton channel. The simultaneous fit of the templates from signal and background events in the lepton + jets and dilepton channels to the data yields a measured top quark mass of M(top) = 172.1 +/- 1.1(stat) +/- 0: 9(syst) GeV/c(2).
Daggett KA, Sakmar TP
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Site-specific in vitro and in vivo incorporation of molecular probes to study G-protein-coupled receptors
CURRENT OPINION IN CHEMICAL BIOLOGY 2011 JUN; 15(3):392-398
Chemical modification of proteins has a rich history in biochemistry and chemical biology. However, studies of membrane protein function, especially in cases where functional expression is low and purification and reconstitution are not feasible, present unique challenges. Heptahelical G-protein-coupled receptors (GPCRs) are a particularly important class of cell-surface receptors that represent targets of more than a quarter of all therapeutic drugs. Understanding with chemical precision how GPCRs function in biological membranes remains a central problem in biology. Recently a number of creative strategies have been developed that allow site-specific attachment of chemical probes or tags directly on expressed receptors or on biologically active peptide ligands or substrates. One particularly important advance is the genetic encoding of unnatural amino acids (UAAs) with unique small bioorthogonal tags using amber codon suppression in mammalian cells. This method should allow site-specific labeling of GPCRs with various molecular probes to facilitate cell-based studies of protein-protein or protein-ligand interactions and the visualization of conformational changes using fluorescence spectroscopy or single-molecule imaging.
Pessach IM, Ordovas-Montanes J, Zhang SY, Casanova JL, Giliani S, Gennery AR, Al-Herz W, Manos PD, Schlaeger TM, Park IH, Rucci F, Agarwal S, Mostoslavsky G, Daley GQ, Notarangelo LD
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Induced pluripotent stem cells: A novel frontier in the study of human primary immunodeficiencies
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 2011 JUN; 127(6):1400-U140
Background: The novel ability to epigenetically reprogram somatic cells into induced pluripotent stem cells (iPSCs) through the exogenous expression of transcription promises to revolutionize the study of human diseases. Objective: Here we report on the generation of 25 iPSC lines from 6 patients with various forms of primary immunodeficiencies (PIDs) affecting adaptive immunity, innate immunity, or both. Methods: Patients' dermal fibroblasts were reprogrammed by expression of 4 transcription factors, octamer-binding transcription factor 4 (OCT4), sex determining region Y-box 2 (SOX2), Krueppel-like factor 4 (KLF4), and cellular myelomonocytosis proto-oncogene (cMYC), by using a single excisable polycistronic lentiviral vector. Results: iPSCs derived from patients with PIDs show a stemness profile that is comparable with that observed in human embryonic stem cells. After in vitro differentiation into embryoid bodies, pluripotency of the patient-derived iPSC lines was demonstrated by expression of genes characteristic of each of the 3 embryonic layers. We have confirmed the patient-specific origin of the iPSC lines and ascertained maintenance of karyotypic integrity. Conclusion: By providing a limitless source of diseased stem cells that can be differentiated into various cell types in vitro, the repository of iPSC lines from patients with PIDs represents a unique resource to investigate the pathophysiology of hematopoietic and extrahematopoietic manifestations of these diseases and might assist in the development of novel therapeutic approaches based on gene correction. (J Allergy Clin Immunol 2011;127:1400-7.)
Chatrchyan S, Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Bergauer T, Dragicevic M, Ero J, Fabjan C, Friedl M, Fruhwirth R, Ghete VM, Hammer J, Hansel S, Hoch M, Hormann N, Hrubec J, Jeitler M, Kasieczka G, Kiesenhofer W, Krammer M, Liko D, Mikulec I, Pernicka M, Rohringer H, Schofbeck R, Strauss J, Teischinger F, Wagner P, Waltenberger W, Walzel G, Widl E, Wulz CE, Mossolov V, Shumeiko N, Gonzalez JS, Benucci L, De Wolf EA, Janssen X, Maes T, Mucibello L, Ochesanu S, Roland B, Rougny R, Selvaggi M, Van Haevermaet H, Van Mechelen P, Van Remortel N, Blekman F, Blyweert S, D'Hondt J, Devroede O, Suarez RG, Kalogeropoulos A, Maes J, Maes M, Van Doninck W, Van Mulders P, Van Onsem GP, Villella I, Charaf O, Clerbaux B, De Lentdecker G, Dero V, Gay APR, Hammad GH, Hreus T, Marage PE, Thomas L, Vander Velde C, Vanlaer P, Adler V, Costantini S, Grunewald M, Klein B, Marinov A, Mccartin J, Ryckbosch D, Thyssen F, Tytgat M, Vanelderen L, Verwilligen P, Walsh S, Zaganidis N, Basegmez S, Bruno G, Caudron J, Ceard L, Gil EC, De Jeneret JD, Delaere C, Favart D, Giammanco A, Gregoire G, Hollar J, Lemaitre V, Liao J, Militaru O, Ovyn S, Pagano D, Pin A, Piotrzkowski K, Schul N, Beliy N, Caebergs T, Daubie E, Alves GA, Damiao DD, Pol ME, Souza MHG, Carvalho W, Da Costa EM, Martins CD, De Souza SF, Mundim L, Nogima H, Oguri V, Da Silva WLP, Santoro A, Do Amaral SMS, Sznajder A, De Araujo FTD, Dias FA, Tomei TRFP, Gregores EM, Lagana C, Marinho F, Mercadante PG, Novaes SF, Padula SS, Darmenov N, Dimitrov L, Genchev V, Iaydjiev P, Piperov S, Rodozov M, Stoykova S, Sultanov G, Tcholakov V, Trayanov R, Vankov I, Dimitrov A, Dyulendarova M, Hadjiiska R, Karadzhinova A, Kozhuharov V, Litov L, Marinova E, Mateev M, Pavlov B, Petkov P, Bian JG, Chen GM, Chen HS, Jiang CH, Liang D, Liang S, Meng X, Tao J, Wang J, Wang J, Wang X, Wang Z, Xiao H, Xu M, Zang J, Zhang Z, Ban Y, Guo S, Guo Y, Li W, Mao Y, Qian SJ, Teng H, Zhang L, Zhu B, Zou W, Cabrera A, Moreno BG, Rios AAO, Oliveros AFO, Sanabria JC, Godinovic N, Lelas D, Lelas K, Plestina R, Polic D, Puljak I, Antunovic Z, Dzelalija M, Brigljevic V, Duric S, Kadija K, Morovic S, Attikis A, Galanti M, Mousa J, Nicolaou C, Ptochos F, Razis PA, Finger M, Finger M, Awad A, Khalil S, Mahmoud MA, Hektor A, Kadastik M, Muntel M, Raidal M, Rebane L, Azzolini V, Eerola P, Czellar S, Harkonen J, Karimaki V, Kinnunen R, Kortelainen MJ, Lampen T, Lassila-Perini K, Lehti S, Linden T, Luukka P, Maenpaa T, Tuominen E, Tuominiemi J, Tuovinen E, Ungaro D, Wendland L, Banzuzi K, Korpela A, Tuuva T, Sillou D, Besancon M, Choudhury S, Dejardin M, Denegri D, Fabbro B, Faure JL, Ferri F, Ganjour S, Gentit FX, Givernaud A, Gras P, de Monchenault GH, Jarry P, Locci E, Malcles J, Marionneau M, Millischer L, Rander J, Rosowsky A, Shreyber I, Titov M, Verrecchia P, Baffioni S, Beaudette F, Benhabib L, Bianchini L, Bluj M, Broutin C, Busson P, Charlot C, Dahms T, Dobrzynski L, Elgammal S, de Cassagnac RG, Haguenauer M, Mine P, Mironov C, Ochando C, Paganini P, Sabes D, Salerno R, Sirois Y, Thiebaux C, Wyslouch B, Zabi A, Agram JL, Andrea J, Bloch D, Bodin D, Brom JM, Cardaci M, Chabert EC, Collard C, Conte E, Drouhin F, Ferro C, Fontaine JC, Gele D, Goerlach U, Greder S, Juillot P, Karim M, Le Bihan AC, Mikami Y, Van Hove P, Fassi F, Mercier D, Baty C, Beauceron S, Beaupere N, Bedjidian M, Bondu O, Boudoul G, Boumediene D, Brun H, Chanon N, Chierici R, Contardo D, Depasse P, El Mamouni H, Falkiewicz A, Fay J, Gascon S, Ille B, Kurca T, Le Grand T, Lethuillier M, Mirabito L, Perries S, Sordini V, Tosi S, Tschudi Y, Verdier P, Megrelidze L, Lomidze D, Anagnostou G, Edelhoff M, Feld L, Heracleous N, Hindrichs O, Jussen R, Klein K, Merz J, Mohr N, Ostapchuk A, Perieanu A, Raupach F, Sammet J, Schael S, Sprenger D, Weber H, Weber M, Wittmer B, Ata M, Bender W, Erdmann M, Frangenheim J, Hebbeker T, Hinzmann A, Hoepfner K, Hof C, Klimkovich T, Klingebiel D, Kreuzer P, Lanske D, Magass C, Merschmeyer M, Meyer A, Papacz P, Pieta H, Reithler H, Schmitz SA, Sonnenschein L, Steggemann J, Teyssier D, Tonutti M, Bontenackels M, Davids M, Duda M, Flugge G, Geenen H, Giffels M, Ahmad WH, Heydhausen D, Kress T, Kuessel Y, Linn A, Nowack A, Perchalla L, Pooth O, Rennefeld J, Sauerland P, Stahl A, Thomas M, Tornier D, Zoeller MH, Martin MA, Behrenhoff W, Behrens U, Bergholz M, Borras K, Cakir A, Campbell A, Castro E, Dammann D, Eckerlin G, Eckstein D, Flossdorf A, Flucke G, Geiser A, Hauk J, Jung H, Kasemann M, Katkov I, Katsas P, Kleinwort C, Kluge H, Knutsson A, Kramer M, Krucker D, Kuznetsova E, Lange W, Lohmann W, Mankel R, Marienfeld M, Melzer-Pellmann IA, Meyer AB, Mnich J, Mussgiller A, Olzem J, Pitzl D, Raspereza A, Raval A, Rosin M, Schmidt R, Schoerner-Sadenius T, Sen N, Spiridonov A, Stein M, Tomaszewska J, Walsh R, Wissing C, Autermann C, Blobel V, Bobrovskyi S, Draeger J, Enderle H, Gebbert U, Kaschube K, Kaussen G, Klanner R, Lange J, Mura B, Naumann-Emme S, Nowak F, Pietsch N, Sander C, Schettler H, Schleper P, Schroder M, Schum T, Schwandt J, Stadie H, Steinbruck G, Thomsen J, Barth C, Bauer J, Buege V, Chwalek T, De Boer W, Dierlamm A, Dirkes G, Feindt M, Gruschke J, Hackstein C, Hartmann F, Heindl SM, Heinrich M, Held H, Hoffmann KH, Honc S, Komaragiri JR, Kuhr T, Martschei D, Mueller S, Muller T, Niegel M, Oberst O, Oehler A, Ott J, Peiffer T, Piparo D, Quast G, Rabbertz K, Ratnikov F, Ratnikova N, Renz M, Saout C, Scheurer A, Schieferdecker P, Schilling FP, Schmanau M, Schott G, Simonis HJ, Stober FM, Troendle D, Wagner-Kuhr J, Weiler T, Zeise M, Zhukov V, Ziebarth EB, Daskalakis G, Geralis T, Karafasoulis K, Kesisoglou S, Kyriakis A, Loukas D, Manolakos I, Markou A, Markou C, Mavrommatis C, Ntomari E, Petrakou E, Gouskos L, Mertzimekis TJ, Panagiotou A, Stiliaris E, Evangelou I, Foudas C, Kokkas P, Manthos N, Papadopoulos I, Patras V, Triantis FA, Aranyi A, Bencze G, Boldizsar L, Hajdu C, Hidas P, Horvath D, Kapusi A, Krajczar K, Radics B, Sikler F, Veres GI, Vesztergombi G, Beni N, Molnar J, Palinkas J, Szillasi Z, Veszpremi V, Raics P, Trocsanyi ZL, Ujvari B, Bansal S, Beri SB, Bhatnagar V, Dhingra N, Gupta R, Jindal M, Kaur M, Kohli JM, Mehta MZ, Nishu N, Saini LK, Sharma A, Singh AP, Singh JB, Singh SP, Ahuja S, Bhattacharya S, Choudhary BC, Gupta P, Jain S, Jain S, Kumar A, Ranjan K, Shivpuri RK, Choudhury RK, Dutta D, Kailas S, Kumar V, Mohanty AK, Pant LM, Shukla P, Aziz T, Guchait M, Gurtu A, Maity M, Majumder D, Majumder G, Mazumdar K, Mohanty GB, Saha A, Sudhakar K, Wickramage N, Banerjee S, Dugad S, Mondal NK, Arfaei H, Bakhshiansohi H, Etesami SM, Fahim A, Hashemi M, Jafari A, Khakzad M, Mohammadi A, Najafabadi MM, Mehdiabadi SP, Safarzadeh B, Zeinali M, Abbrescia M, Barbone L, Calabria C, Colaleo A, Creanza D, De Filippis N, De Palma M, Fiore L, Iaselli G, Lusito L, Maggi G, Maggi M, Manna N, Marangelli B, My S, Nuzzo S, Pacifico N, Pierro GA, Pompili A, Pugliese G, Romano F, Roselli G, Selvaggi G, Silvestris L, Trentadue R, Tupputi S, Zito G, Abbiendi G, Benvenuti AC, Bonacorsi D, Braibant-Giacomelli S, Brigliadori L, Capiluppi P, Castro A, Cavallo FR, Cuffiani M, Dallavalle GM, Fabbri F, Fanfani A, Fasanella D, Giacomelli P, Giunta M, Grandi C, Marcellini S, Masetti G, Meneghelli M, Montanari A, Navarria FL, Odorici F, Perrotta A, Rossi AM, Rovelli T, Siroli G, Travaglini R, Albergo S, Cappello G, Chiorboli M, Costa S, Tricomi A, Tuve C, Barbagli G, Ciulli V, Civinini C, D'Alessandro R, Focardi E, Frosali S, Gallo E, Gonzi S, Lenzi P, Meschini M, Paoletti S, Sguazzoni G, Tropiano A, Benussi L, Bianco S, Colafranceschi S, Fabbri F, Piccolo D, Fabbricatore P, Musenich R, Benaglia A, De Guio F, Di Matteo L, Ghezzi A, Malberti M, Malvezzi S, Martelli A, Massironi A, Menasce D, Moroni L, Paganoni M, Pedrini D, Ragazzi S, Redaelli N, Sala S, de Fatis TT, Tancini V, Buontempo S, Montoya CAC, Cavallo N, Cimmino A, De Cosa A, Fabozzi F, Iorio AOM, Lista L, Merola M, Noli P, Paolucci P, Azzi P, Bacchetta N, Bellan P, Bisello D, Branca A, Carlin R, Checchia P, De Mattia M, Dorigo T, Dosselli U, Fanzago F, Gasparini F, Gasparini U, Lacaprara S, Lazzizzera I, Margoni M, Mazzucato M, Meneguzzo AT, Nespolo M, Perrozzi L, Pozzobon N, Ronchese P, Simonetto F, Torassa E, Tosi M, Vanini S, Zotto P, Zumerle G, Berzano U, Ratti SP, Riccardi C, Torre P, Vitulo P, Biasini M, Bilei GM, Caponeri B, Fano L, Lariccia P, Lucaroni A, Mantovani G, Menichelli M, Nappi A, Romeo F, Santocchia A, Taroni S, Valdata M, Volpe R, Azzurri P, Bagliesi G, Bernardini J, Boccali T, Broccolo G, Castaldi R, D'Agnolo RT, Dell'Orso R, Fiori F, Foa L, Giassi A, Kraan A, Ligabue F, Lomtadze T, Martini L, Messineo A, Palla F, Palmonari F, Segneri G, Serban AT, Spagnolo P, Tenchini R, Tonelli G, Venturi A, Verdini PG, Barone L, Cavallari F, Del Re D, Di Marco E, Diemoz M, Franci D, Grassi M, Longo E, Nourbakhsh S, Organtini G, Palma A, Pandolfi F, Paramatti R, Rahatlou S, Amapane N, Arcidiacono R, Argiro S, Arneodo M, Biino C, Botta C, Cartiglia N, Castello R, Costa M, Demaria N, Graziano A, Mariotti C, Marone M, Maselli S, Migliore E, Mila G, Monaco V, Musich M, Obertino MM, Pastrone N, Pelliccioni M, Romero A, Ruspa M, Sacchi R, Sola V, Solano A, Staiano A, Trocino D, Pereira AV, Belforte S, Cossutti F, Della Ricca G, Gobbo B, Montanino D, Penzo A, Heo SG, Nam SK, Chang S, Chung J, Kim DH, Kim GN, Kim JE, Kong DJ, Park H, Ro SR, Son D, Son DC, Kim Z, Kim JY, Song S, Choi S, Hong B, Jeong MS, Jo M, Kim H, Kim JH, Kim TJ, Lee KS, Moon DH, Park SK, Rhee HB, Seo E, Shin S, Sim KS, Choi M, Kang S, Kim H, Park C, Park IC, Park S, Ryu G, Choi Y, Choi YK, Goh J, Kim MS, Kwon E, Lee J, Lee S, Seo H, Yu I, Bilinskas MJ, Grigelionis I, Janulis M, Martisiute D, Petrov P, Sabonis T, Castilla-Valdez H, De La Cruz-Burelo E, Lopez-Fernandez R, Sanchez-Hernandez A, Villasenor-Cendejas LM, Moreno SC, Valencia FV, Ibarguen HAS, Linares EC, Pineda AM, Reyes-Santos MA, Krofcheck D, Tam J, Butler PH, Doesburg R, Silverwood H, Ahmad M, Ahmed I, 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Search for physics beyond the standard model in opposite-sign dilepton events in pp collisions at root s=7 TeV
JOURNAL OF HIGH ENERGY PHYSICS 2011 JUN; ?(6):? Article 026
A search is presented for physics beyond the standard model (SM) in final states with opposite-sign isolated lepton pairs accompanied by hadronic jets and missing transverse energy. The search is performed using LHC data recorded with the CMS detector, corresponding to an integrated luminosity of 34 pb(-1). No evidence for an event yield beyond SM expectations is found. An upper limit on the non-SM contribution to the signal region is deduced from the results. This limit is interpreted in the context of the constrained minimal supersymmetric model. Additional information is provided to allow testing the exclusion of specific models of physics beyond the SM.
Schober M, Fuchs E
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Tumor-initiating stem cells of squamous cell carcinomas and their control by TGF-beta and integrin/focal adhesion kinase (FAK) signaling
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2011 JUN 28; 108(26):10544-10549
Cancer stem cells (CSCs) sustain tumor growth through their ability to self-renew and to generate differentiated progeny. These functions endow CSCs with the potential to initiate secondary tumors bearing characteristics similar to those of the parent. Recently the hair follicle stem cell marker CD34 was used to purify a CSC-like cell population from early skin tumors arising from treatment with 7,12-dimethylbenz[alpha] anthracene/12-o-tetradecanoylphorbol-13-acetate, which typically generates benign papillomas that occasionally progress to squamous cell carcinomas (SCCs). In the present study, we identify and characterize CSCs purified from malignant SCCs. We show that SCCs contain two highly tumorigenic CSC populations that differ in CD34 levels but are enriched for integrins and coexist at the SCC-stroma interface. Intriguingly, whether CD34(Io) or CD34(hi), alpha 6(hi)beta 1(hi) populations can initiate secondary tumors by serial limitdilution transplantation assays, but alpha 6(io)beta 1(io) populations cannot. Moreover, secondary tumors generated from a single CSC of either subtype contain both CD34(Io) and CD34(hi) alpha 6(hi)beta 1(hi)CSCs, indicating their nonhierarchical organization. Genomic profiling and hierarchical cluster analysis show that these two CSC subtypes share a molecular signature distinct from either the CD34(-) epidermal or the CD34hi hair follicle stem cell signature. Although closely related, alpha 6(hi)beta 1(hi)CD34(Io) and alpha 6(hi)beta 1(hi)CD34(hi) CSCs differ in cell-cycle gene expression and proliferation characteristics. Indeed, proliferation and expansion of alpha 6(hi)beta 1(hi)CD34(hi) CSCs is sensitive to whether they can initiate a TGF-beta receptor II-mediated response to counterbalance elevated focal adhesion kinase-mediated integrin signaling within the tumor. Overall, the coexistence and interconvertibility of CSCs with differing sensitivities to their microenvironment pose challenges and opportunities for SCC cancer therapies.
Maldonado M, Kapoor TM
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Moving Right Along: How PP1 Helps Clear the Checkpoint
DEVELOPMENTAL CELL 2011 JUN 14; 20(6):733-734
Spindle checkpoint silencing is crucial for cell-cycle progression, but mechanisms underlying this process remain mysterious. Two papers, one in this issue of Developmental Cell (Meadows et al., 2011) and one in Current Biology (Rosenberg et al., 2011), begin to show how phosphatase PP(-)I -gamma connects chromosome-microtubule attachment with anaphase entry.
Field MC, Sali A, Rout MP
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On a bender-BARs, ESCRTs, COPs, and finally getting your coat
JOURNAL OF CELL BIOLOGY 2011 JUN 13; 193(6):963-972
Tremendous variety in form and function is displayed among the intracellular membrane systems of different eukaryotes. Until recently, few clues existed as to how these internal membrane systems had originated and diversified. However, proteomic, structural, and comparative genomics studies together have revealed extensive similarities among many of the protein complexes used in controlling the morphology and trafficking of intracellular membranes. These new insights have had a profound impact on our understanding of the evolutionary origins of the internal architecture of the eukaryotic cell.
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Search for new physics with same-sign isolated dilepton events with jets and missing transverse energy at the LHC
JOURNAL OF HIGH ENERGY PHYSICS 2011 JUN; ?(6):? Article 077
The results of searches for new physics in events with two same-sign isolated leptons, hadronic jets, and missing transverse energy in the final state are presented. The searches use an integrated luminosity of 35 pb(-1) of pp collision data at a centre-of-mass energy of 7TeV collected by the CMS experiment at the LHC. The observed numbers of events agree with the standard model predictions, and no evidence for new physics is found. To facilitate the interpretation of our data in a broader range of new physics scenarios, information on our event selection, detector response, and efficiencies is provided.
Twist KA, Husnain SI, Franke JD, Jain D, Campbell EA, Nickels BE, Thomas MS, Darst SA, Westblade LF
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A novel method for the production of in vivo-assembled, recombinant Escherichia coli RNA polymerase lacking the alpha C-terminal domain
PROTEIN SCIENCE 2011 JUN; 20(6):986-995
The biochemical characterization of the bacterial transcription cycle has been greatly facilitated by the production and characterization of targeted RNA polymerase (RNAP) mutants. Traditionally, RNAP preparations containing mutant subunits have been produced by reconstitution of denatured RNAP subunits, a process that is undesirable for biophysical and structural studies. Although schemes that afford the production of in vivo-assembled, recombinant RNAP containing amino acid substitutions, insertions, or deletions in either the monomeric beta or beta' subunits have been developed, there is no such system for the production of in vivo-assembled, recombinant RNAP with mutations in the homodimeric alpha-subunits. Here, we demonstrate a strategy to generate in vivo-assembled, recombinant RNAP preparations free of the alpha C-terminal domain. Furthermore, we describe a modification of this approach that would permit the purification of in vivo-assembled, recombinant RNAP containing any alpha-subunit variant, including those variants that are lethal. Finally, we propose that these related approaches can be extended to generate in vivo-assembled, recombinant variants of other protein complexes containing homomultimers for biochemical, biophysical, and structural analyses.